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Targeting multiple oncogenic pathways for the treatment of hepatocellular carcinoma

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Abstract

Hepatocellular carcinoma (HCC) is one of the most common forms of liver cancer diagnosed worldwide. HCC occurs due to chronic liver disease and is often diagnosed at advanced stages. Chemotherapeutic agents such as doxorubicin are currently used as first-line agents for HCC therapy, but these are non-selective cytotoxic molecules with significant side effects. Sorafenib, a multi-targeted tyrosine kinase inhibitor, is the only approved targeted drug for HCC patients. However, due to adverse side effects and limited efficacy, there is a need for the identification of novel pharmacological drugs beyond sorafenib. Several agents that target and inhibit various signaling pathways involved in HCC are currently being assessed for HCC treatment. In the present review article, we summarize the diverse signal transduction pathways responsible for initiation as well as progression of HCC and also the potential anticancer effects of selected targeted therapies that can be employed for HCC therapy.

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Authors and Affiliations

  1. Department of Biotechnology, JSS Science and Technology University, JSS Technical Institutions Campus, Mysore, Karnataka, 570006, India

    Supritha G. Swamy, Vivek H. Kameshwar & Nanjunda Swamy Shivananju

  2. Department of Studies in Chemistry, University of Mysore, Manasagangotri, Mysore, 570 006, Karnataka, India

    Priya B. Shubha

  3. Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, 50603, Malaysia

    Chung Yeng Looi

  4. Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117597, Singapore

    Muthu K. Shanmugam & Gautam Sethi

  5. School of Biomedical Sciences, Curtin Health Innovation Research Institute, Biosciences Research Precinct, Curtin University, Bentley, Western Australia, 6009, Australia

    Frank Arfuso, Arunasalam Dharmarajan & Gautam Sethi

  6. Department of Pharmaceutical Sciences, College of Pharmacy, Larkin Health Sciences Institute, 18301 N. Miami Avenue, Miami, FL, 33169, USA

    Anupam Bishayee

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  1. Supritha G. Swamy
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  2. Vivek H. Kameshwar
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  7. Arunasalam Dharmarajan
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  8. Gautam Sethi
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  9. Nanjunda Swamy Shivananju
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Corresponding authors

Correspondence to Nanjunda Swamy Shivananju or Anupam Bishayee.

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Funding

This work was supported by a SERB Fast Track Research Grant (SB/FT/LS-297/2012) to NSS, by a NUHS Bench-to-Bedside grant to GS, by a University Malaya research grant (RP027C-14HTM), and by a University Malaya High Impact research grant (H-20001-E00002) awarded to CYL.

Conflict of Interest

SGS, VHK, PBS, CYL, MKS, FA, AD, GS, NSS and AB declare no conflict of interest.

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Swamy, S.G., Kameshwar, V.H., Shubha, P.B. et al. Targeting multiple oncogenic pathways for the treatment of hepatocellular carcinoma. Targ Oncol 12, 1–10 (2017). https://doi.org/10.1007/s11523-016-0452-7

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